Can [18F]3F4AP detect brain demyelination? Evaluation of novel PET tracer in nonhuman primates and humans

项目摘要 脱髓鞘是多发性硬化症（MS）的标志，也存在于其他疾病中 包括脑缺血、创伤性脑损伤甚至阿尔茨海默病。目前，脱髓鞘 主要使用MRI对疾病进行成像。尽管MRI对脱髓鞘高度敏感， 它不能定量区分脱髓鞘与其他潜在的并发症的病理过程 如炎症或轴突缺失。正电子发射断层扫描（PET）可以提供定量和 生化特异性信息来补充MRI。 我们最近根据FDA批准的MS 4药物开发了一种用于脱髓鞘的PET放射性示踪剂， 氨基吡啶（4AP），称为[18F]3F4AP。我们发现这种示踪剂可用于检测啮齿动物的脱髓鞘 它是MS的模型，并且它具有成像猴子大脑的良好特性。在这个项目中，我们力求 研究这种示踪剂在创伤性脑损伤模型中用于成像脱髓鞘的潜力， 在非人类灵长类动物和人类身上进行验证。这里收集的信息对于设计和 对未来人类研究的解释。一旦得到验证，这种示踪剂将有助于更好地监测 脱髓鞘疾病和逆转脱髓鞘的疗法的开发。

Project Summary Demyelination represents the hallmark of multiple sclerosis (MS) and is also present in other diseases including brain ischemia, traumatic brain injury and even Alzheimer’s disease. Currently, demyelinating diseases are primarily imaged using MRI. Even though MRI is highly sensitive to demyelination, it is not quantitative and it cannot distinguish demyelination from other potentially coexisiting pathological processes such as inflammation or axonal loss. Positron Emission Tomography (PET) can provide quantitative and biochemically specific information to complement MRI. We recently developed a PET radiotracer for demyelination based on the FDA-approved drug for MS 4- aminopyridine (4AP) called [18F]3F4AP. We showed that this tracer be used to detect demyelination in rodent models of MS and that it has good properties for imaging the brain in monkeys. In this project, we seek to investigate the potential of this tracer for imaging demyelination in a model of traumatic brain injury and to validate it in nonhuman primates and humans. The information gathered here will be crucial for the design and interpretation of future human studies. Once validated, this tracer and could contribute to better monitoring of demyelinating diseases and to the development of therapies to reverse demyelination.